A comparative study of the lateral geniculate body of rat (Rattus norvegicus), bat (Eidolon helvum) and pangolin (Manis tricuspis).

In this study, the lateral geniculate bodies (LGB) of rats, bats and pangolins were compared using histological and quantitative histochemical parameters to observe possible modifications that enable these mammals to cope with their habitation particularly with respect to their diet. The study was conducted using ten adult Wistar rats, ten fruit bats and eight pangolins comprising of both sexes. After being sacrificed by cervical dislocation, their skulls were opened using bone forceps to expose the brains. The lateral geniculate bodies were excised from each brain tissue, homogenized and homogenate studied spectrophotometrically for the activities of lactate dehydrogenase (LDH), glucose-6-phosphate dehydrogenase (G-6-PDH), acid phosphatase (ACP), alkaline phosphatase (ALP) and acetylcholinesterase (AChE). The LGB tissue samples meant for histological studies were fixed in 10% formol calcium and processed for paraffin wax embedding. Serial sections of 3?m thickness were stained with Hematoxylin and Eosin (H & E) and Cresyl fast violet (CFV) stains. The stained tissues were studied under the light microscope. Application of one-way ANOVA statistical method showed that there were significant differences (p<0.05) in the activities of LDH, G-6-PDH, ACP, ALP and AChE of the LGB of the three mammals as revealed in the quantitative histochemistry of these enzymes and markers. Histological observations revealed no observable differences in the relative distribution of neurons and their supporting glial cells within the LGB of the three mammalian species. The comparison of the differences observed in the histological and the quantitative histochemical activities in these mammalian species revealed a variation in the visual perception and their individual peculiarities in relation to their mode and pattern of living.

Age-related changes in nitric oxide synthase in the lateral geniculate nucleus of rats.

Age-related changes in nitric oxide production in the visual system have not been well characterized. Therefore, we used staining and image-processing approaches to describe changes in levels of neuronal nitric oxide synthase (nNOS), the NADPH-diaphorase (NADPH-d) histochemical marker, and 3-nitrotyrosine in the lateral geniculate nucleus (LGN) of young and aged rats. The LGN plays an important role in the visual system, as it acts as a visual relay nucleus. Quantitative analysis of NADPH-d-positive and nNOS-immunoreactive neurons revealed significant optical density increases in the dorsal LGN and ventral LGN of aged rats; however, no significant changes were observed in the number of neurons with age. 3-Nitrotyrosine immunoreactivity was increased in the dorsal LGN and ventral LGN of aged rats. These results indicate that increased nitric oxide production and peroxynitrite may be associated with alterations in visual function during aging.

Some aspects of the modular organization of the primary visual cortex of the cat: patterns of cytochrome oxidase activity.

The distribution of the enzyme cytochrome oxidase (CO) in continuous series of parasagittal sections from field 17 and frontal sections of the dorsal nucleus of the lateral geniculate body (LGB) from normal kittens and adult cats was studied. In all cats apart from neonates, layer IV showed regularly alternating areas with above-background levels of CO activity ("spots"). There was a significant increase in the contrast of the "spots" from days 13 to 21, which was followed by a significant decrease from days 48 to 93. These changes coincided with ontogenetic changes in the level of visual system plasticity. There were no differences in CO activity between layers A and A1 of the dorsal nucleus of the LGB. It is suggested that the non-uniform distribution of the level of functional activity of neurons in field 17 reflects the formation of columnar cortical structures during the critical period of postnatal ontogenesis.

Neuronal death in the lateral geniculate nucleus of young ferrets following a cortical lesion: time-course, age dependence and involvement of caspases.

In humans and many other mammalian species, the behavioural consequences of a cortical lesion tend to be milder when it occurs early in life, and there is evidence that an important factor contributing to the behavioural sparing in the young is the formation of new thalamo-cortical connections by thalamic neurons initially connected with the lesioned area. However, this plasticity may be hindered by the secondary death of many of these neurons owing to the elimination by the primary lesion of their trophic support from the cortex. With the long-term aim of preventing this neuronal death, we have here characterised its timing in the lateral geniculate nucleus of ferrets following lesions of the visual cortex on postnatal days 5, 10, 20 or 35. After the earliest lesions (P5 or P10), this cell death began rapidly and occurred synchronously, being maximal at 48 h and declining to zero over the next few days. Following later lesions the cell death began more slowly and continued for longer. The dying neurons contained activated caspase-3 and fragmented DNA and their number 2 days after a P5 lesion was reduced by the broad-band caspase inhibitor z-VAD.fmk. These experiments open the way for a concerted effort to enhance adaptive plasticity by neuroprotection in the hours or days following a cortical lesion.

Identification of subdivisions in the medial geniculate body of the guinea pig.

The accurate and reliable identification of subdivisions within the auditory thalamus is important for future studies of this nucleus. However, in the guinea pig, there has been no agreement on the number or nomenclature of subdivisions within the main nucleus of the auditory thalamus, the medial geniculate body (MGB). Thus, we assessed three staining methods in the guinea pig MGB and concluded that cytochrome oxidase (CYO) histochemistry provides a clear and reliable method for defining MGB subdivisions. By combining CYO with acetylcholinesterase staining and extensive physiological mapping we defined five separate divisions, all of which respond to auditory stimuli. Coronal sections stained for CYO revealed a moderate to darkly-stained oval core. This area (the ventral MGB) contained a high proportion (61%) of V-shaped tuning curves and a tonotopic organisation of characteristic frequencies. It was surrounded by four smaller areas that contained darkly stained somata but had a paler neuropil. These areas, the dorsolateral and suprageniculate (which together form the dorsal MGB), the medial MGB and the shell MGB, did not have any discernable tonotopic frequency gradient and contained a smaller proportion of V-shaped tuning curves. This suggests that CYO permits the identification of core and belt areas within the guinea pig MGB.

Intraocular delivery of BDNF following visual cortex lesion upregulates cytosolic branched chain aminotransferase (BCATc) in the rat dorsal lateral geniculate nucleus.

Visual cortex ablation in newborn rats determines the almost complete degeneration of neurons in the dorsal lateral geniculate nucleus (dLGN), as a consequence of the axotomy of the geniculo-cortical fibres. Death of dLGN neurons is massive and rapid, and occurs by apoptosis. We recently showed that exogenous administration of the neurotrophin brain-derived neurotrophic factor (BDNF) in the eye prevents the degeneration of dLGN neurons occurring after visual cortex lesion in newborn rats. To elucidate the molecular mechanisms of BDNF-mediated neuroprotection, we sought to identify novel genes regulated by BDNF in the rat dLGN after visual cortex lesion. By using mRNA fingerprinting, we isolated a cDNA fragment upregulated in the dLGN of lesioned rats treated with BDNF. This cDNA fragment shared 100% homology with the rat cytosolic branched chain aminotransferase (BCATc), a key enzyme of glutamate metabolism. Quantitative reverse transcription-polymerase chain reaction and in situ hybridization confirmed that BCATc mRNA is markedly overexpressed by exogenous supply of BDNF to axotomized dLGNs. Immunohistochemical analysis showed that upregulation of BCATc in the dLGN of lesioned rats treated with BDNF takes place in astrocytes. These results suggest that modulation of glutamate metabolism by astrocytes might play an important role in BDNF-mediated survival of axotomized dLGN neurons.

Circadian change in tryptophan hydroxylase protein levels within the rat intergeniculate leaflets and raphe nuclei.

Serotonin (5-HT) is involved in the synchronisation of the mammalian circadian clock located in the suprachiasmatic nuclei of the hypothalamus (SCN). This clock is synchronised by light (photic cues) and by non-photic cues. Non-photic cues are notably conveyed to the SCN by a direct 5-HT pathway arising from the mesencephalic median raphe nucleus (MRN). Furthermore, an indirect projection conveys non-photic inputs by 5-HT fibres from the mesencephalic dorsal raphe nucleus (DRN) to the intergeniculate leaflets of the thalamus (IGL) which project to the SCN. In the rat, the quantitative distribution of tryptophan hydroxylase (TpH), used as an index of 5-HT synthesis, was studied by in situ immunoautoradiography in both the serotoninergic cell bodies area of the raphe nuclei and the serotoninergic terminal field of the IGL. Under a 12 h light: 12 h dark (LD 12:12), TpH protein amount exhibited a rhythmic variation within the IGL. The maximum levels were reached at the day/night transition. In both MRN and the lateral groups of the DRN, TpH variations were opposite to those observed in the IGL. Such phase opposition was reported previously in the MRN/SCN pathway and was correlated with a rhythmic release of 5-HT within the SCN [Eur J Neurosci 15 (2002) 833]. Thus, the daily rhythmicity of TpH levels observed in DRN-IGL pathway may be correlated with a rhythmic release of 5-HT in the IGL at the beginning of the night. Under constant darkness, TpH rhythmic variations in the two serotoninergic pathways were maintained and similar to those observed under light/dark cycle. These results demonstrate the existence of a circadian endogenous functioning in the 5-HT neurones projecting to the rat circadian system.

Thalamocortical cells in the cat pulvinar nucleus transiently express nitric oxide synthase during development.

We examined the postnatal expression of the neuronal form of nitric oxide synthase (nNOS) within the pulvinar and lateral posterior (LP) nuclei of the cat thalamus using immunocytochemical techniques. During the first postnatal month, nNOS was expressed in many cells within the pulvinar nucleus and medial subdivision of the LP nucleus; fewer neurons in the lateral LP nucleus were stained by the nNOS antibody. We examined the pulvinar nucleus to determine what cell types express nNOS. A comparison of the soma sizes of nNOS-stained cells to the overall population of Nissl-stained cells and interneurons (stained with an antibody against glutamic acid decarboxylase) suggests that within the pulvinar nucleus, thalamocortical cells express nNOS during development. In addition, the nNOS antibody stained axon bundles that traverse the pulvinar nucleus to enter the optic radiations, suggesting that thalamocortical cell axons also contain nNOS during development. However, this staining pattern was dramatically reduced by postnatal day 42 and later ages; the size of the remaining nNOS-stained cells was closer to that of interneurons, a subset of which contain nNOS in the adult pulvinar nucleus. This contrasts with our previous findings that nNOS is specifically expressed within interneurons in the developing dorsal lateral geniculate nucleus (LGN) and serves as further confirmation that the pulvinar nucleus and LGN represent distinct categories of thalamic nuclei.

Brain nitric oxide synthase expression in the developing ferret lateral geniculate nucleus: analysis of time course, localization, and synaptic contacts.

Nitric oxide (NO) is a diffusible neurotransmitter that has been implicated in key developmental events, including the refinement of retinogeniculate axons into ON/OFF sublayers in the ferret lateral geniculate nucleus (LGN), and in the formation of eye-specific laminae in other species. To understand the role of NO in the LGN, it is critical to fully characterize the pattern of brain nitric oxide synthase (bNOS) expression within the nucleus, including the phenotype of the neural elements that express it. We have examined the temporal and spatial pattern of bNOS expression in the ferret LGN during the first 6 weeks of postnatal development, and in the adult, by detecting bNOS with a monoclonal antibody as well as beta-nicotinamide adenine dinucleotide phosphate-diaphorase histochemistry. We have found that bNOS is expressed in neurons in the A laminae of the LGN as early as postnatal day 7 (P7), a time coincident with eye-specific segregation of retinal axons. This expression continues through P35, with peak somatodendritic expression at P21. Fluorescent double labeling using antibodies to bNOS and glutamic acid decarboxylase indicate that bNOS is expressed in gamma-aminobutyric acid-ergic interneurons within the A laminae. Electron microscopic examination of bNOS-labeled cells showed synaptic contacts from terminals with two distinct morphologic profiles. Expression of bNOS within interneurons that receive contacts from multiple sources indicates that the synaptic circuitry associated with bNOS activation and the potential targets of NO may be more complex than originally thought and supports a potential new role for interneurons as cellular intermediaries in the refinement of pathways in the LGN. Our findings broaden the window of time that bNOS may be active within the developing LGN, suggesting an expanded role for NO during early postnatal development.

Adenylate cyclase 1 as a key actor in the refinement of retinal projection maps.

cAMP occupies a strategic position to control neuronal responses to a large variety of developmental cues. We have analyzed the role of calcium-stimulated adenylate cyclase 1 (AC1) in the development of retinal topographic maps. AC1 is expressed in retinal ganglion cells (RGCs) from embryonic day 15 to adulthood with a peak during the first postnatal week. At that time, the other calcium-stimulated AC, AC8, is expressed in the superior colliculus (SC) but not in the RGCs. In mice of the barrelless strain, which carry an inactivating mutation of the AC1 gene, calcium-stimulated AC activity is reduced by 40-60% in the SC and retina. RGC projection maps were analyzed with a variety of anterograde and retrograde tracers. After an initially normal development until postnatal day 3, retinal fibers from the ipsilateral and contralateral eye fail to segregate into eye-specific domains in the lateral geniculate nucleus and the SC. Topographic defects in the fine tuning of the retinotectal and retinogeniculate maps are also observed with abnormalities in the confinement of the retinal axon arbors in the anteroposterior and mediolateral dimensions. This is attributable to the lack of elimination of misplaced axon collaterals and to the maintenance of a transient ipsilateral projection. These results establish an essential role of AC1 in the fine patterning of the retinal map. Calcium-modulated cAMP production in the RGCs could constitute an important link between activity-dependent changes and the anatomical restructuring of the retinal terminal arbors within central targets.

Multifaceted roles of nitric oxide in the lateral geniculate nucleus: from visual signal transduction to neuronal apoptosis.

The lateral geniculate nucleus (LGN) is the thalamic relay of retinal inputs to the visual cortex. It contains a rich array of brain terminals, which modulate the visual signals to the cortex. Several data have documented that beside cholinergic, GABA-nergic, istaminergic, serotoninergic, and glutamatergic signals, the LGN contains also fibers and interneurons expressing the enzyme that produces nitric oxide (NO). Here, we review the documented physiological roles of NO in the transmission of visual inputs to the cortex and in the processes of activity-dependent refinement of LGN connections. Moreover we focus on the recently suggested role of NO in processes of neurotoxicity in the LGN. Particular relevance is given to studies documenting that, through an excitotoxic cascade, NO triggers apoptosis in the LGN of new-born rats deprived of vision in one eye. Data are also discussed on a possible role of NO in the mechanisms of LGN neuronal loss induced by glaucoma. We believe that a better understanding of the role of NO in the LGN may contribute to discover new experimental strategies for the treatment of degenerative ophthalmic diseases.

[Histochemical studies on the change of nitric oxide synthetase in lateral geniculate nucleus of monocular deprived kittens].

OBJECTIVE: To observe the change of nitric oxide synthetase (NOS) in lateral geniculate nucleus of normal and monocular deprived kittens and to discuss the role of nitric oxide in the etiopathology of amblyopia. METHODS: The distribution of nitric oxide synthetase in lateral geniculate nucleus (LGN) of normal and monocular deprived kittens had been studied by using nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase histochemical method (NDP). RESULTS: In normal kittens, NOS positive cells were not seen in any lamina of LGN, but NOS positive fibers were discovered. In monocular deprived kittens, NOS positive fibers were seen in every layers of LGN, in the nondeprived laminae of LGN there was strip-shaped distribution of NOS positive cells, and in the deprived laminae the NOS positive cells were occasionally seen. CONCLUSION: NOS might act as a new class of neurotransmitter and be involved in the formation of emblyopia.

Striate cortex in dichromatic and trichromatic marmosets: neurochemical compartmentalization and geniculate input.

The superficial layers of primate striate cortex (V1) contain a regular pattern of dense staining for cytochrome oxidase (CO) reactivity ("blobs") that receive direct input from the koniocellular layers of the lateral geniculate nucleus. It has been suggested that the blob regions are dedicated to processing color information. Here, the neurochemical compartmentalization of blobs and their input from the lateral geniculate nucleus (LGN) was measured in marmosets (Callithrix jacchus) identified as having either dichromatic or trichromatic color vision. In all animals, layer III of V1 showed a patchy distribution of CO. The spatial density of CO blobs (mean, 4.6 blobs/mm(2); range, 3.9-5.5), blob diameter, and the proportion of cortical area within blobs was not significantly different in dichromats and trichromats. The LGN input was studied by injecting retrograde tracer into V1. The koniocellular layers of the LGN contribute 11% of all relay cells, and form the only geniculate input to upper layer III of V1. Only half of all relay cells in the KC layers express calbindin. There is no obvious difference between dichromats and trichromats in the pattern of the geniculate projection to V1. It is concluded that the trichromatic phenotype is not associated with changes in the gross anatomy, neurochemistry, or organization of the geniculate afferents to the superficial layers of V1.

C-fos and c-jun expressions in nitric oxide synthase immunoreactive neurons in the lateral geniculate nucleus of experimental glaucomatous rats.

The present study was initiated to investigate the expressions of c-fos and c-jun in nitric oxide synthase immunoreactive neurons and their possible roles in the lateral geniculate nucleus (LGN) of glaucomatous rats. An experimental one-eye glaucoma model was created by cauterisation of the limbal-derived veins. Animals were killed by cardiac perfusion, and brains containing the LGN were removed and processed for c-fos, c-jun and neuronal nitric oxide synthase (nNOS) immunohistochemistry. No c-fos or c-jun immunoreactivity was observed in the LGN of control rats. In the glaucomatous rats, expression of c-fos and c-jun was induced bilaterally in the ventral LGN (vLGN) as early as 2 h postoperation. The number of c-fos-immunopositive cells increased at 1 and 2 days postoperation in both the lateral and medial subdivisions of the vLGN (vLGN-l and vLGN-m). Thereafter, the expression decreased and was totally absent at 1 and 2 weeks. No c-fos was induced in the dorsal LGN (dLGN). C-jun-immunopositive cells were mainly localised in the intergeniculate leaflet and vLGN. Few neurons were observed in the dLGN. The number of c-jun-immunopositive cells decreased at 1 and 2 weeks postoperation. Some of the c-fos- and c-jun-immunopositive cells were also nNOS immunopositive. The present results reveal that glaucoma activates the expressions of immediate early genes (IEGs) in some cells of the LGN. It is postulated that they may play important roles in the pathologic processes of glaucoma. The relationship between these IEGs and nitric oxide was also discussed.

Retinofugal projections in the short-tailed opossum (Monodelphis domestica).

In the current investigation, retinofugal projections to midbrain and thalamic nuclei of Monodelphis domestica were investigated using wheat-germ agglutinin conjugated to horseradish peroxidase (WGA-HRP). Large intraocular injections of WGA-HRP were placed into the eye, and patterns of labeled axon terminals were related to nuclear boundaries in tissue that was stained for Nissl or reacted for cytochrome oxidase (CO). Our results demonstrate that the major projection from the retina is to the contralateral dorsal lateral geniculate nucleus (LGNd) and the superior colliculus (SC). Connections were also observed with the contralateral pretectal nucleus (PRT), the lateral posterior nucleus (LP), and the ventral division of the lateral geniculate nucleus (LGNv). Ipsilateral connections were with the LGNv and LGNd. These findings are consistent with reports in other marsupials as well as with studies in a number of eutherian mammals. Thus, there appears to be a common pattern of retinofugal projections that all mammals share, probably due to retention from a common ancestor. However, some features such as a lack of ipsilateral input to the SC (which are absent only in certain species like Monodelphis, platypus, and echidnas) may represent a primitive state retained from a common ancestor. When comparisons of retinofugal connections and LGNd organization are made across taxa, three types of organization are observed: a homogenous LGNd with a high degree of binocular overlap of projections; a partially differentiated LGNd with some segregation of eye-specific inputs; and a fully segregated structure with a large degree of segregation of eye-specific inputs. We discuss the factors that contribute to the organization observed in extant mammals and conclude that phylogeny and lifestyle appear to be the underlying factors contributing to the organization of the LGNd.

Developmental regulation of brain nitric oxide synthase expression in the ferret thalamic reticular nucleus.

We have found that cells in the ferret thalamic reticular nucleus (TRN) express brain nitric oxide synthase (bNOS) in a transient pattern during early postnatal development. Similar to our previous findings in the lateral geniculate nucleus (LGN), bNOS expression in the TRN is first observed at postnatal day 7 (P7) and continues to P35. Quantitative measures show a significant change in the relative numbers of bNOS+ cells from P7-P35, and suggest there is a transition in morphology from a bipolar shape with two primary dendrites, to a more complex, multipolar arrangement. During TRN development, the pattern of bNOS expression shifts from the somatodendritic localization seen during the first postnatal month to expression within axon fibers in the adult. Expression of bNOS within TRN cells demonstrates an additional source of nitric oxide in the developing visual thalamus, perhaps indicating a common function for thalamic nitergic neurons as cellular mediators in the establishment of central topography both in the LGN and the TRN.

Glaucoma in primates: cytochrome oxidase reactivity in parvo- and magnocellular pathways.

PURPOSE: To evaluate the differential effects of ganglion cell depletion from experimental glaucoma on the relative metabolic activities of neurons in the parvo (P)- and magno (M)-cellular visual pathways of the macaque visual system. METHODS: Monocular experimental glaucoma was induced in monkeys (Macaca mulatta and M. fascicularis) by applying a laser to the trabecular meshwork to increase intraocular pressure (IOP). After other behavioral and electrophysiological studies, the lateral geniculate nuclei (LGNs) and the primary visual cortices were analyzed for functional afference from surviving ganglion cells, indicated by cytochrome oxidase (CO) histochemistry. RESULTS: CO reactivity (COR) indicated a general reduction in neural metabolism with increasing severity of glaucoma. COR in the LGNs was reduced to the same degree in both the P- and M-cellular layers. In layer 4Cbeta of the V1 cortex, the reactivity was always reduced more than in the layer 4Calpha division. CONCLUSIONS: Experimental glaucoma in monkeys reduces visual afference to the central nervous system, thereby reducing the metabolic drive as indicated by COR. The detrimental effect of glaucoma did not appear to be any greater for the M-cell, rather than the P-cell pathway in the LGN or in the visual cortex. Both are affected by the duration and severity of the experimental glaucoma. Overall, the alterations in metabolism of neurons in the parallel visual pathways supplied by the Palpha and Pbeta ganglion cells do not suggest that tests based on the functional properties of one or the other would provide optimal assessment of glaucoma.

The distribution of NADPH diaphorase and nitric oxide synthetase (NOS) in relation to the functional compartments of areas V1 and V2 of primate visual cortex.

The primary visual cortex (V1) of primates receives visual signals from cells in the koniocellular (K), magnocellular (M) and parvocellular (P) layers of the lateral geniculate nucleus (LGN). The functional role of the K pathway is unknown, but one proposal is that it modulates visual activity locally via release of nitric oxide (NO). One goal of this study was to examine the distribution of nitric oxide synthetase (NOS), the enzyme that produces NO, using immunocytochemistry for brain NOS (bNOS) or histochemistry for nicotinamide adenine dinucleotide phosphate (NADPH) diaphorase activity in the V1 target cells of the K pathway and within the LGN itself. A second goal was to examine bNOS and NADPH diaphorase activity within proposed functional compartments in the second visual area (V2). We examined the LGN, V1 and V2 in squirrel monkeys, owl monkeys and bushbabies. In V1 and V2, we found that dense neuropil staining for NADPH diaphorase mirrored the pattern of high metabolic activity shown with cytochrome oxidase (CO) staining but did not necessarily mirror the pattern of immunolabeling seen with antibodies against NOS. The smooth stellate cells stained for NADPH diaphorase or bNOS were sparse and did not colocalize with LGN recipient zones in V1 or with the CO compartments in V2. LGN cells projecting to V1, including K, M and P cells, were negative for bNOS and NADPH diaphorase. Therefore, high levels of NOS are not limited to the K pathway. Instead, dense NOS activity is present in interneurons and within the neuropil of V1 and V2 that exhibit high metabolic demand.

Human COX6A1 gene: promoter analysis, cDNA isolation and expression in the monkey brain.

The human COX6A1 gene encodes the ubiquitous isoform of cytochrome c oxidase (COX) subunit VIa (VIa-L), and is located in a CpG island on chromosome 12q24.2. We compared the COX6A1 gene with the published cDNA and several ESTs and concluded that subunit COX VIa-L is synthesized as a preprotein, as are other COX subunits. The same transcription start sites were identified by primer extension analysis of human brain and lymphoblastoid RNA. Analysis of the COX6A1 promoter revealed several conserved sequence elements found in other COX genes, namely binding sites for nuclear respiratory factor 1 (NRF-1), nuclear respiratory factor 2/GA binding protein (NRF-2/GABP), and ying-yang protein 1 (YY1). These conserved elements were shown to bind nuclear proteins from HeLa nuclear extracts. COX6A1 cDNA was isolated from a human brain cDNA library, and the sequence was identical to that of human liver. The expression of this gene was demonstrated by in-situ hybridization in monkey brain sections with our human brain cDNA. Monocular impulse blockade in adult monkeys induced a downregulation of COX6A1 expression in deprived visual neurons, suggesting that this subunit gene is regulated by neuronal activity.

NOS inhibition during postnatal development leads to increased ipsilateral retinocollicular and retinogeniculate projections in rats.

Synthesis of nitric oxide (NO) occurs downstream from activation of N-methyl-D-aspartate (NMDA) receptors; NO reportedly acts as a retrograde messenger, influencing the refinement and stabilization of coactive afferent terminals. Cells and neuropil in the rat superior colliculus (SC) and lateral geniculate body (LGB) show intense, developmentally regulated activity for NO synthase (NOS). To study the role of NO in the development of retinogeniculate and retinotectal axon arbors, we examined primary visual projections of rats that had received intraperitoneal injections of Nomega-nitro-L-arginine (L-NoArg, an NOS inhibitor) on postnatal day 0, and daily thereafter for 4-6 weeks. Treated rats showed significant alterations in ipsilateral retinotectal projections, in the mediolateral and anteroposterior axes; there was an increase in the density of fibres entering the SC, in branch length, and in the numbers of boutons on retinotectal arbors in the treated group. Ipsilaterally projecting retinal axons also showed an increase in density and distribution in the dorsal nucleus of the LGB. If animals were allowed to survive for several months after stopping treatment, similar changes were also noted, but these were much less striking. Our results support the hypothesis that, in the mammalian visual system, NO released from target neurons in the SC and LGB serves as a retrograde signal which feeds back on retinal afferents, influencing their growth. The effects of NOS inhibition are partially reversed after treatment is stopped, indicating that lack of NO synthesis delays the maturation of retinofugal connections, and also that NO plays a constitutive role in their development.